The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury

Neel R. Sodha, Richard T. Clements, Jun Feng, Yuhong Liu, Cesario Bianchi, Eszter M. Horvath, Csaba Szabo, Frank W. Sellke

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Objective: Ischemia-reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H2S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H2S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.

Original languageEnglish (US)
Pages (from-to)906-913
Number of pages8
JournalEuropean Journal of Cardio-thoracic Surgery
Volume33
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Therapeutic Uses
Sulfides
Reperfusion Injury
Apoptosis
Reperfusion
Caspase 3
Apoptosis Inducing Factor
Staining and Labeling
Ischemia
In Situ Nick-End Labeling
Necrosis
Hemodynamics
Myocardial Reperfusion Injury
Evans Blue
Hydrogen Sulfide
Troponin I
Therapeutics
Adenosine Diphosphate
Infarction
Myocardial Ischemia

Keywords

  • Apoptosis
  • Cardiac
  • Ischemia
  • Protection
  • Reperfusion
  • Sulfide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Sodha, N. R., Clements, R. T., Feng, J., Liu, Y., Bianchi, C., Horvath, E. M., ... Sellke, F. W. (2008). The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. European Journal of Cardio-thoracic Surgery, 33(5), 906-913. https://doi.org/10.1016/j.ejcts.2008.01.047

The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. / Sodha, Neel R.; Clements, Richard T.; Feng, Jun; Liu, Yuhong; Bianchi, Cesario; Horvath, Eszter M.; Szabo, Csaba; Sellke, Frank W.

In: European Journal of Cardio-thoracic Surgery, Vol. 33, No. 5, 05.2008, p. 906-913.

Research output: Contribution to journalArticle

Sodha, Neel R. ; Clements, Richard T. ; Feng, Jun ; Liu, Yuhong ; Bianchi, Cesario ; Horvath, Eszter M. ; Szabo, Csaba ; Sellke, Frank W. / The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. In: European Journal of Cardio-thoracic Surgery. 2008 ; Vol. 33, No. 5. pp. 906-913.
@article{c46391a6bc2a478684bcd6459bf79e5b,
title = "The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury",
abstract = "Objective: Ischemia-reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H2S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H2S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size ({\%} of AAR) in controls was 47.4 ± 6.2{\%} vs 20.1 ± 3.3{\%} in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0{\%} (p = 0.10) and 45.1{\%} (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.",
keywords = "Apoptosis, Cardiac, Ischemia, Protection, Reperfusion, Sulfide",
author = "Sodha, {Neel R.} and Clements, {Richard T.} and Jun Feng and Yuhong Liu and Cesario Bianchi and Horvath, {Eszter M.} and Csaba Szabo and Sellke, {Frank W.}",
year = "2008",
month = "5",
doi = "10.1016/j.ejcts.2008.01.047",
language = "English (US)",
volume = "33",
pages = "906--913",
journal = "European Journal of Cardio-thoracic Surgery",
issn = "1010-7940",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury

AU - Sodha, Neel R.

AU - Clements, Richard T.

AU - Feng, Jun

AU - Liu, Yuhong

AU - Bianchi, Cesario

AU - Horvath, Eszter M.

AU - Szabo, Csaba

AU - Sellke, Frank W.

PY - 2008/5

Y1 - 2008/5

N2 - Objective: Ischemia-reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H2S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H2S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.

AB - Objective: Ischemia-reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H2S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H2S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.

KW - Apoptosis

KW - Cardiac

KW - Ischemia

KW - Protection

KW - Reperfusion

KW - Sulfide

UR - http://www.scopus.com/inward/record.url?scp=41949101867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41949101867&partnerID=8YFLogxK

U2 - 10.1016/j.ejcts.2008.01.047

DO - 10.1016/j.ejcts.2008.01.047

M3 - Article

C2 - 18314343

AN - SCOPUS:41949101867

VL - 33

SP - 906

EP - 913

JO - European Journal of Cardio-thoracic Surgery

JF - European Journal of Cardio-thoracic Surgery

SN - 1010-7940

IS - 5

ER -